The present study set out to investigate the clinical significance of CVF tests in glaucomatous eyes. The sum of thresholds obtained with the red target was significantly higher in all four regions in glaucomatous eyes. Similarly, the sum of thresholds obtained with the blue-purple target was higher in all regions except the PMB. Furthermore, 50% of patients under 50 years old, who did not have any abnormalities in the central 4 points indicated by SAP, showed a significant increase in at least one CVF threshold value of the central 4 points.
It has been reported that large retinal nerve fibers are damaged early in glaucoma [20–23]. In retinal ganglion cells, K cells (small bistratified cells), which have spectral features at short wavelengths, have 50% larger cell bodies than P cells (midget cells), which have spectral features at medium to long (M/L) wavelengths [24]. K cells account for a small proportion of all ganglion cells and are considered to be less redundant, making them susceptible to early damage due to glaucoma. A visual function test that utilizes this characteristic is short-wavelength automated perimetry (SWAP), in which the M/L cones are suppressed by presenting a background of strong yellow light, and the function of only the S cones is tested by presenting a blue target. Because SWAP can detect K-cell damage, it is considered able to detect glaucomatous visual field defects earlier than conventional visual-field testing [10–11]. There are several disadvantages of SWAP: age-related yellowing of the lens may block blue light [25–27]; the test is prone to problems of variability and unreliability [28–29]; the background color during the test is a strong yellow light of 200 cd/m2; and the test takes a long time, which causes subject fatigue. In recent years, programs with shorter examination times have been developed to reduce fatigue[13], but improvements have yet to be obtained in reproducibility and in countering the effects of cataracts.
The CVF test introduced here is a test that presents targets with the same luminance as the achromatic background color D65. Red and blue-purple were used as the target hues, and retinal sensitivity was measured by changing the size of the target without changing the saturation. In the CVA test[17] (which was the basis of this CVF test) was a visual acuity test with different hues, and the visual acuity of both blue-purple and yellow-green was clearly worse than for other colors. In addition, since there are no blue cones at the center of the fovea[30] and the two colors and the background color are on the color confusion locus of tritanopia (Fig. 2, right), the CVA report[17] considered that the two colors stimulate blue cones. Similarly, the red and blue-green colors that produced the best visual acuity also stimulate L/M cones because they are on the same confusion locus in protanopia [Figure 2, left].
A test similar to the CVF or CVA test is the cone contrast test [31], which can measure retinal function separately for S/M/L cones. This is a test that measures retinal sensitivity by measuring the threshold value with low saturation without changing brightness or hue, and without changing the size of a presenting letter, and we speculate that the principle is very similar to that of the test used in the study reported here. The reason for placing 16 measurement points within 5 degrees of the center in the CVF test is that the distribution of S cones is reported to be concentrated within 3 degrees of the center [32–34]. Since the overall number of measurement points is small, the CVF examination time is about 5 minutes per color per eye, which helps to reduce fatigue in the examinees.
In glaucoma, vision is impaired along the axons of retinal ganglion cells (RGCs), so there is a difference in visual field impairment above and below the macula. In addition, it has been reported that there are many RGCs in the macular region and the PMB region, where visual field defects are less likely to occur[30]. Therefore, in the present study, the parameters obtained were divided into 4 areas: 8 upper and 8 lower points, 4 central points, and 10 PMB points, and compared with normal eyes. The results here show that detection of both the red and blue-purple targets was significantly higher in the glaucomatous eye than in the normal eye.
The reason why glaucoma could be detected with red is unclear. However, it might be explained by the fact that the eyes had already been determined to have visual field abnormalities using SAP, and that damage to the retinal ganglion P cells had already occurred. It will be necessary to examine the difference in results from preperimetric glaucoma, which shows fewer visual-field defects. Also, as a result of measurement of the 4 central points (expected to be subject to less measurement error), in 50% of eyes without abnormalities as measured by SAP, a deviation of 2 SD or more from the normal CVF was observed. This seems to suggest the possibility that the CVF test can detect visual-field abnormalities earlier than SAP.
The current study had several limitations. The glaucomatous eyes tested were more myopic than normal eyes. Myopia is one of the risk factors for glaucoma, and the longer the axial length of the eye, the higher the prevalence and relative risk of glaucoma [35, 36]. As a result, the number of patients with myopic tendencies increased in glaucoma case selection. It has also been reported that myopia itself reduces retinal sensitivity [37, 38], and the impact of this sensitivity reduction on the comparison of normal and glaucomatous eyes in the present study could not be excluded. In addition, the aging-related yellowing of the crystalline lens must also be considered in CVF examination of the blue-purple target. In the present study, even in normal eyes aged 60 years or older, some measurement points were unresponsive despite presenting the maximum value of the blue-purple target. To avoid the effects of cataracts, subjects aged ≥ 80 years or those with a nuclear hardness of ≥ 3 were excluded, but there were no strict exclusion criteria such as a contrast visual acuity test, which may have affected the results. In future research, it will be necessary to examine the reproducibility of color vision testing with age.
In conclusion, CVF with red and blue-purple targets was detectably worse in eyes with glaucoma, and the abnormality was confirmed even in regions judged as normal using SAP,implying that this test may be more sensitive than SAP. In addition, the CVF test places less burden on the patient than SAP, there are fewer test points, and the test time is short. Therefore, in the future, CVF testing may become a preferred tool for detecting glaucoma.